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Team finds gene that promotes drug resistance in cancer
Date:1/14/2013

unique to myeloma; this is basically seen in every single cancer we looked at."

Taking the findings back to the lab, the team then examined the effect on cancer cells of either enhancing or blocking the expression of the NEK2 gene.

"Our studies show that over-expression of NEK2 in cancer cells significantly enhances the activity of drug efflux proteins to pump chemotherapy drugs out of cells, resulting in drug resistance. Furthermore, silencing NEK2 in cancer cells potently decreased drug resistance, induced cell-cycle arrest, cell death, and inhibited cancer cell growth in vitro and in vivo," says Zhan, UI professor of internal medicine.

The research team is now developing compounds to inhibit NEK2 by collaborating with David Bearss, Ph.D., associate professor of physiology and developmental biology at BYU, in the hope that these compounds may overcome drug resistance in cancer cells.

"We were able to show that if we inhibit NEK2, then we can actually restore sensitivity to drugs that we use right now," Bearss says.

Although development and clinical testing of such drugs for use in patients is not imminent, Tricot notes that the findings may have clinical use within the next several years.

"NEK2 expression may be a diagnostic or prognostic marker for drug-resistant cancer," he says. "If NEK2 is high, that would suggest that the prognosis is poorer and the patient might benefit from more aggressive treatment. The other potential use is for monitoring the cancer's response to therapy. If NEK2 levels increase, that would suggest development of increased drug resistance and might indicate that a change of treatment would be helpful."


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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-356-7124
University of Iowa Health Care
Source:Eurekalert

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